The present invention relates to the use of glycolipids and specific catchers therefore in treatment of diabetes.
Galactosylceramide is a glycolipid consisting of ceramide to which galactose is attached. It is made by the enzyme ceramide galactosyltransferase which binds its two parts together. Galactosylceramide is a precursor of sulfatide and is present in the neural system and in islets of Langerhans in small amounts. A sulfatransferase enzyme is able to attach sulfate to the galactose group and thereby to convert galactosylceramide to sulfatide. It is a possibility that galactosylceramide given in vivo is converted to sulfatide. However, galactosylceramide may also act by itself and, indeed effects of galactosylceramide have been described in vitro (Buschard, K., Diamant, M., Bovin, L. F., Fredman, P., Bendtzen, K., Sulphatide and its precursor, galactosylceramide, influence the production of cytokines in human mononuclear cells. APMIS 104: 938-944, 1996). It has been shown that galactosylceramide can modulate and mainly enhance the production of different cytokines from both monocytes and T-cells after stimulation with LPS and PHA, respectively.
Most importantly TNF and IL-6 production is increased compared to incubation with LPS and PHA without galactosylceramide.
Glucosylceramide and lactosylceramide are related glycolipids which likely have the same effects as galactosylceramide.
The present invention relates to the use of a glycolipid or a specific catcher thereof for the production of a pharmaceutical preparation for treatment of prediabetes, diabetes and/or associated complications in an individual.
Furthermore, the invention relates to glycolipids, in particular galactosylceramide, glucosylceramide and lactosylceramide, and specific catchers therefore (antibodies or lectins) for use in the prophylaxis or therapy of prediabetes, diabetes and/or associated complications in an individual.
The invention also relates to a specific catcher for the glycolipids according to the invention, said catcher being a monoclonal antibody against galactosylceramide, glucosylceramide or lactosylceramide.
The invention also relates to a method for preventing the development of prediabetes, diabetes and/or associated complications in an individual, wherein a glycolipid, in particular galactosylceramide, glucosylceramide or lactosylceramide, is administered to said individual, preferably at its perinatal stage.
The characterising features or the invention will be evident from the following description and the appended claims.
As stated above, the invention relates glycolipids, in particular galactosylceramide, glucosylceramide and lactosylceramide, and specific catchers therefore (antibodies or lectins) for use in the prophylaxis or therapy of prediabetes, diabetes and/or associated complications in an individual, as well as to the use of a glycolipid or a specific catcher thereof for the production of a pharmaceutical preparation for treatment of prediabetes, diabetes and/or associated complications in an individual.
The expression xe2x80x9ctreatmentxe2x80x9d used herein relates to both the prophylaxis of said conditions in an individual being in risk of developing any of the conditions and to the therapeutic treatment of an individual who have already developed any of the conditions.
The prophylactic treatment is performed by inducing tolerance to the antigenic glycolipids. When the glycolipids, the specific catchers therefore and/or the pharmaceutical preparation according to the invention is used for this purpose they are preferably administered perinatally to said individual.
The glycolipid used according to the invention is preferably galactosylceramide, glucosylceramide or lactosylceramide. The specific catcher used according to the invention is preferably an antibody or a lectin, and more preferably a monoclonal antibody against galactosylceramide, glucosylceramide or lactosylceramide.
The glycolipid, the specific catcher or the pharmaceutical preparation according to the invention may be administered in any suitable way known to the man skilled in the art. Preferably, they are administered nasally, orally, subcutaneously, intramuscularly, or intravenously.
The glycolipids or the pharmaceutical preparation may lead to increased levels of suppressor or regulator cells or antibodies against lymphocytes recognising the antigenic glycolipids in said individual. Alternatively, they may lead to the removal of antibodies and/or lymphocytes recognising the antigenic glycolipids from the blood stream of the individual.
It may be suitable to administer the glycolipids according to the invention together with bacterial adjuvants. The pharmaceutical composition according to the invention may therefore also comprises a least one bacterial adjuvant, such as cholera, staphyloccoc or galactosylceramide (alpha-form) of bacterial origin.
The pharmaceutical preparation according to the invention may also comprise substances used to facilitate the production of the pharmaceutical preparation or the administration of the preparations. Such substances are well known to people skilled in the art and may for example be pharmaceutically acceptable adjuvants, carriers and preservatives.
When antibodies are used according to the invention they will lead to an increase of anti-antibodies in said individual.
The invention also relates to a method for preventing the development of prediabetes, diabetes and/or associated complications in an individual, wherein a glycolipid, in particular galactosylceramide, glucosylceramide or lactosylceramide, is administered to said individual, preferably at its perinatal stage.
The method may be performed by removing lymphocytes from the individual, contact the lymphocytes with a glycolipid, in particular galactosylceramide, glucosylceramide or lactosylceramide, in vitro to make them recognise this antigen, irradiating them to inhibit their cytotoxicity, and (a) returning them to the individual to raise suppressor or regulator cells or antibodies against lymphocytes reactive with this antigen, or (b) administering them parenterally to another mammal in order to raise antibodies against lymphocytes reactive with this antigen in said mammal and then isolating serum containing the antibodies from said mammal and administering it to the individual.
The method may also be performed by contacting the blood stream of the individual with an immobilised glycolipid, in particular galactosylceramide, glucosylceramide or lactosylceramide, to remove antibodies and/or lymphocytes recognising the antigenic glycolipids from the individual.
Finally, it is also possible to perform the method by parenterally administer an antibody against glycolipids, in particular galactosylceramide, glucosylceramide or lactosylceramide, (a) to said individual in a sufficient amount to raise anti-antibodies in said individual, or (b) to another mammal in order to raise anti-antibodies in said mammal and then isolating serum containing the anti-antibodies from said mammal and administering it to the individual.